Retinoic acid and its rearranged receptor in the etiology and treatment of acute promyelocytic leukemia.

All-trans retinoic acid can induce complete remissions in patients with acute promyelocytic leukemia. The balanced chromosomal translocation t(15;17)(q22;q12-21) of this malignancy is now known to involve the nuclear retinoic acid receptor-alpha (RAR-alpha) on the long arm of chromosome 17 and a novel gene on the long arm of chromosome 15, designated PML (previously called myl). A unique fusion mRNA, PML/RAR-alpha, is produced. Paradoxically, this rearrangement of RAR-alpha results in clinical sensitivity to retinoic acid. Despite its efficacy, retinoic acid therapy has side effect, including a syndrome of hyperleukocytosis and respiratory distress in some patients. Remissions induced and maintained by continuous all-trans-retinoic treatment are not durable in most of these patients. Retinoic acid therapy for acute promyelocytic leukemia represents a unique example where a molecular defect may be involved both in the pathogenesis and treatment of a malignancy.